The guinea pig adrenal cortex is made up of four zones which are morphologically distinct and respond in different ways to suppression and stimulation (Black, 1972; Black and Bogart, 1973; Black and Russo, 1978; Black et al., 1978). These adrenals are capable not only of producing several different steroid hormones but also of metabolizing steroids in the ring A position and of metabolizing xenobiotic compounds (Greiner et al., 1976a,b). Several of these functions have been shown to change with age and to differ in males and females (Greiner et al., 1976b, 1977). It is the purpose of this study to determine by the combined techniques of morphometry, biochemistry, tissue culture and somatic cell genetics, using whole adrenals and separated zonal cell types: 1) If the zones are specialized with regard to these various functions and change independently with age. 2) What factors in the hormonal milieu influence the changes with age and sex. 3) What factors in the cells effect the functional differences between zones, if any, between sexes and with age: plasma membrane ACTH receptors, microsomal enzyme activation, microsomal membrane composition, gene expression.